INHIBITION OF RAT RENAL AND TESTICULAR 11-BETA-HYDROXYSTEROID DEHYDROGENASE BY SOME ANTIHYPERTENSIVE DRUGS, DIURETICS, AND EPITESTOSTERONE

With regard to previous finding of an inhibitory activity of furosemid e on 11 beta-hydroxysteroid dehydrogenase, 16 other commonly used diur etics have been tested as to their ability to inhibit rat renal, and i n four instances also testicular 11 beta-hydroxysteroid dehydrogenase, using glycyrrhetinic acid as a standard. In addition, epitestosterone has been tested as well, with respect to its recently demonstrated in hibitory activity on several other enzymes of androgen biosynthesis. B esides corticosterone, 11 beta-hydroxy-4-androstene-3,17-dione has bee n used as a substrate. Of all drugs studied, quinapril, dihydralazin, trandolapril, metipamid, methyldopa, betaxolol only appeared to be wea k inhibitors of 11 beta-hydroxysteroid dehydrogenase, with an inhibito ry activity 10-28% of that of glycyrrhetinic acid. Using corticosteron e as a substrate, epitestosterone displayed a weak inhibitory activity with K-i 850, 1200 nmol/l and V-max 2420, 3900 nmol/l.min for renal a nd testicular enzyme, respectively. In contrast to kidneys, the testic ular 11 beta-hydroxysteroid dehydrogenase accepted also 11 beta-hydrox y-4-androstene-3,17-dione as a substrate, which could be inhibited by epitestosterone (K-i 1490 nmol/l, V-max 1150 nmol/l.min). The results represent further evidence for different substrate specificity of rena l and testicular 11 beta-hydroxysteroid dehydrogenase.